Aerobic Base-free C-H Bond Activation at a Pd Center in Aqueous Conditions

Abstract

Recent reports have increasingly documented palladium-catalyzed C-H bond functionalization reactions involving high-valent Pd^III and Pd^IV intermediates, yet these transformations often depend on strong oxidants and external bases. Herein, we report a series of Pd(II) complexes [(^pRN3CH)Pd^II(MeCN)](BF₄)₂, supported by a tetradentate pyridinophane ligand, that undergo aerobic C-H bond activation under mild aqueous conditions without the need for an added external base to generate isolable Pd^III complexes. In this transformation, O₂ serves as both an oxidant and proton acceptor, eliminating the need for an exogenous base. Mechanistic and computational studies are consistent with a rate-limiting concerted metalation-deprotonation (CMD) pathway involving a key Pd-O₂ species that promotes the C-H bond activation step. Notably, the presence of water in the solvent mixture and slightly elevated temperatures enhance reactivity and lead to quantitative formation of the Pd^III product, improving its synthetic utility. Overall, this study establishes a C–H bond activation pathway at high-valent palladium centers that proceeds without added external base, with O₂ serving as both oxidant and internal proton acceptor. These findings provide key insights into high-valent palladium reactivity and lay a mechanistic foundation for sustainable aerobic oxidation strategies.